Substance P and vasoactive intestinal peptide are reduced in right transverse colon in pediatric slow-transit constipation

Authors

  • S. K. King,

    1. Department of General Surgery, Royal Children’s Hospital, Melbourne, Australia
    2. Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia
    3. Department of Paediatrics, University of Melbourne, Melbourne, Australia
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  • J. R. Sutcliffe,

    1. Department of General Surgery, Royal Children’s Hospital, Melbourne, Australia
    2. Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia
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  • S.-y. Ong,

    1. Department of Paediatrics, University of Melbourne, Melbourne, Australia
    2. Gut Motility Laboratory, Murdoch Childrens Research Institute, Melbourne, Australia
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  • M. Lee,

    1. Department of Paediatrics, University of Melbourne, Melbourne, Australia
    2. Gut Motility Laboratory, Murdoch Childrens Research Institute, Melbourne, Australia
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  • T. L. Koh,

    1. Department of Paediatrics, University of Melbourne, Melbourne, Australia
    2. Gut Motility Laboratory, Murdoch Childrens Research Institute, Melbourne, Australia
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  • S. Q. Wong,

    1. Department of Paediatrics, University of Melbourne, Melbourne, Australia
    2. Gut Motility Laboratory, Murdoch Childrens Research Institute, Melbourne, Australia
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  • P. J. Farmer,

    1. Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia
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  • C. J. Peck,

    1. Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia
    2. Gut Motility Laboratory, Murdoch Childrens Research Institute, Melbourne, Australia
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  • M. P. Stanton,

    1. Department of General Surgery, Royal Children’s Hospital, Melbourne, Australia
    2. Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia
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  • J. Keck,

    1. Department of Colorectal Surgery, St Vincent’s Hospital, Melbourne, Australia
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  • D. J. Cook,

    1. Department of Medical Imaging, Royal Children’s Hospital, Melbourne, Australia
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  • C. W. Chow,

    1. Department of Paediatrics, University of Melbourne, Melbourne, Australia
    2. Department of Anatomical Pathology, Royal Children’s Hospital, Melbourne, Australia
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  • J. M. Hutson,

    1. Department of General Surgery, Royal Children’s Hospital, Melbourne, Australia
    2. Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia
    3. Department of Paediatrics, University of Melbourne, Melbourne, Australia
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  • B. R. Southwell

    1. Surgical Research Group, Murdoch Childrens Research Institute, Melbourne, Australia
    2. Gut Motility Laboratory, Murdoch Childrens Research Institute, Melbourne, Australia
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Address for Correspondence
Dr. Bridget R. Southwell, Gut Motility Laboratory, Surgical Research Group, Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Victoria 3052, Australia.
Tel: 61 3 9345 5069; fax: 61 3 9345 7997;
e-mail: bridget.southwell@mcri.edu.au

Abstract

Background  Slow-transit constipation (STC) is recognized in children but the etiology is unknown. Abnormalities in substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide (NO) have been implicated. The density of nerve fibers in circular muscle containing these transmitters was examined in colon from children with STC and compared to other pediatric and adult samples.

Methods  Fluorescence immunohistochemistry using antibodies to NO synthase (NOS), VIP and SP was performed on colonic biopsies (transverse and sigmoid colon) from 33 adults with colorectal cancer, 11 children with normal colonic transit and anorectal retention (NAR) and 51 with chronic constipation and slow motility in the proximal colon (STC). The percentage area of nerve fibers in circular muscle containing each transmitter was quantified in confocal images.

Key Results  In colon circular muscle, the percentage area of nerve fibers containing NOS > VIP > SP (6 : 2 : 1). Pediatric groups had a higher density of nerve fibers than adults. In pediatric samples, there were no regional differences in NOS and VIP, while SP nerve fiber density was higher in sigmoid than proximal colon. STC children had lower SP and VIP nerve fiber density in the proximal colon than NAR children. Twenty-three percent of STC children had low SP nerve fiber density.

Conclusions & Inferences  There are age-related reductions in nerve fiber density in human colon circular muscle. NOS and VIP do not show regional variations, while SP nerve fiber density is higher in distal colon. 1/3 of pediatric STC patients have low SP or VIP nerve fiber density in proximal colon.

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